Advanced brain age in deployment-related traumatic brain injury: A LIMBIC-CENC neuroimaging study.

OBJECTIVE: To determine if history of mild traumatic brain injury (mTBI) is associated with advanced or accelerated brain aging among the United States (US) military Service Members and Veterans. METHODS: Eight hundred and twenty-two participants (mean age = 40.4 years, 714 male/108 female) underwent MRI sessions at eight sites across the US. Two hundred and one participants completed a follow-up scan between five months and four years later. Predicted brain ages were calculated using T1-weighted MRIs and then compared with chronological ages to generate an Age Deviation Score for cross-sectional analyses and an Interval Deviation Score for longitudinal analyses. Participants also completed a neuropsychological battery, including measures of both cognitive functioning and psychological health. RESULT: In cross-sectional analyses, males with a history of deployment-related mTBI showed advanced brain age compared to those without (t(884) = 2.1, p = .038), while this association was not significant in females. In follow-up analyses of the male participants, severity of posttraumatic stress disorder (PTSD), depression symptoms, and alcohol misuse were also associated with advanced brain age. CONCLUSION: History of deployment-related mTBI, severity of PTSD and depression symptoms, and alcohol misuse are associated with advanced brain aging in male US military Service Members and Veterans.

Microstructural Organization of Distributed White Matter Associated With Fine Motor Control in US Service Members With Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is the most common form of brain injury. While most individuals recover from mTBI, roughly 20% experience persistent symptoms, potentially including reduced fine motor control. We investigate relationships between regional white matter organization and subcortical volumes associated with performance on the Grooved Pegboard (GPB) test in a large cohort of military Service Members and Veterans (SM&Vs) with and without a history of mTBI(s). Participants were enrolled in the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. SM&Vs with a history of mTBI(s) (n = 847) and without mTBI (n = 190) underwent magnetic resonance imaging and the GPB test. We first examined between-group differences in GPB completion time. We then investigated associations between GPB performance and regional structural imaging measures (tractwise diffusivity, subcortical volumes, and cortical thickness) in SM&Vs with a history of mTBI(s). Lastly, we explored whether mTBI history moderated associations between imaging measures and GPB performance. SM&Vs with mTBI(s) performed worse than those without mTBI(s) on the non-dominant hand GPB test at a trend level (p < 0.1). Higher fractional anisotropy (FA) of tracts including the posterior corona radiata, superior longitudinal fasciculus, and uncinate fasciculus were associated with better GPB performance in the dominant hand in SM&Vs with mTBI(s). These findings support that the organization of several white matter bundles are associated with fine motor performance in SM&Vs. We did not observe that mTBI history moderated associations between regional FA and GPB test completion time, suggesting that chronic mTBI may not significantly influence fine motor control.

The Effect of Intranasal Plus Transcranial Photobiomodulation on Neuromuscular Control in Individuals with Repetitive Head Acceleration Events.

Objective: This proof-of-concept study was to investigate the relationship between photobiomodulation (PBM) and neuromuscular control. Background: The effects of concussion and repetitive head acceleration events (RHAEs) are associated with decreased motor control and balance. Simultaneous intranasal and transcranial PBM (itPBM) is emerging as a possible treatment for cognitive and psychological sequelae of brain injury with evidence of remote effects on other body systems. Methods: In total, 43 (39 male) participants, age 18-69 years (mean, 49.5; SD, 14.45), with a self-reported history of concussive and/or RHAE and complaints of their related effects (e.g., mood dysregulation, impaired cognition, and poor sleep quality), completed baseline and posttreatment motor assessments including clinical reaction time, grip strength, grooved pegboard, and the Mini Balance Evaluation Systems Test (MiniBEST). In the 8-week interim, participants self-administered itPBM treatments by wearing a headset comprising four near-infrared light-emitting diodes (LED) and a near-infrared LED nasal clip. Results: Posttreatment group averages in reaction time, MiniBEST reactive control subscores, and bilateral grip strength significantly improved with effect sizes of g = 0.75, g = 0.63, g = 0.22 (dominant hand), and g = 0.34 (nondominant hand), respectively. Conclusion: This study provides a framework for more robust studies and suggests that itPBM may serve as a noninvasive solution for improved neuromuscular health.

White Matter Hyperintensities and Mild TBI in Post-9/11 Veterans and Service Members.

INTRODUCTION: The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. MATERIALS AND METHODS: The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median postinjury interval of 8 years) or negative mTBI history (n = 198), were examined. RESULTS: White matter hyperintensities were present in both mTBI and comparison groups at similar rates (39% and 37%, respectively). There was an age-by-diagnostic group interaction, such that older Veterans and Service Members with a history of mTBI demonstrated a significant increase in the number of WMHs present compared to those without a history of mTBI. Additional associations between an increase in the number of WMHs and service-connected disability, insulin-like growth factor-1 levels, and worse performance on tests of episodic memory and executive functioning-processing speed were found. CONCLUSIONS: Subtle but important clinical relationships are identified when larger samples of mTBI participants are used to examine the relationship between history of head injury and radiological findings. Future studies should use follow-up magnetic resonance imaging and longitudinal neurobehavioral assessments to evaluate the long-term implications of WMHs following mTBI.

Intimate Partner Violence-Related Brain Injury: Unmasking and Addressing the Gaps.

Intimate partner violence (IPV) is a significant, global public health concern. Women, individuals with historically underrepresented identities, and disabilities are at high risk for IPV and tend to experience severe injuries. There has been growing concern about the risk of exposure to IPV-related head trauma, resulting in IPV-related brain injury (IPV-BI), and its health consequences. Past work suggests that a significant proportion of women exposed to IPV experience IPV-BI, likely representing a distinct phenotype compared with BI of other etiologies. An IPV-BI often co-occurs with psychological trauma and mental health complaints, leading to unique issues related to identifying, prognosticating, and managing IPV-BI outcomes. The goal of this review is to identify important gaps in research and clinical practice in IPV-BI and suggest potential solutions to address them. We summarize IPV research in five key priority areas: (1) unique considerations for IPV-BI study design; (2) understanding non-fatal strangulation as a form of BI; (3) identifying objective biomarkers of IPV-BI; (4) consideration of the chronicity, cumulative and late effects of IPV-BI; and (5) BI as a risk factor for IPV engagement. Our review concludes with a call to action to help investigators develop ecologically valid research studies addressing the identified clinical-research knowledge gaps and strategies to improve care in individuals exposed to IPV-BI. By reducing the current gaps and answering these calls to action, we will approach IPV-BI in a trauma-informed manner, ultimately improving outcomes and quality of life for those impacted by IPV-BI.

Regional brain volume prior to treatment is linked to outcome after cognitive rehabilitation in traumatic brain injury.

Cognitive rehabilitation is useful for many after traumatic brain injury (TBI), but we lack critical knowledge about which patients benefit the most from different approaches. Advanced neuroimaging techniques have provided important insight into brain pathology and systems plasticity after TBI, and have potential to inform new practices in cognitive rehabilitation. In this study, we aimed to identify candidate structural brain measures with relevance for rehabilitation of cognitive control (executive) function after TBI. Twenty-eight patients (9 female, mean age 40.5 (SD = 13.04) years) with TBI (>21 months since injury) that participated in a randomized controlled cognitive rehabilitation trial (NCT02692352) were included in the analyses. Regional brain volume was extracted from T1-weighted MRI scans before treatment using tensor-based morphometry. Both positive and negative associations between treatment outcome (everyday cognitive control function) and regional brain volume were observed. The most robust associations between regional brain volume and improvement in function were observed in midline fronto-parietal regions, including the anterior and posterior cingulate cortices. The study provides proof of concept and valuable insight for planning future studies focusing on neuroimaging in cognitive rehabilitation after TBI.

Coordinating Global Multi-Site Studies of Military-Relevant Traumatic Brain Injury: Opportunities, Challenges, and Harmonization Guidelines.

Traumatic brain injury (TBI) is common among military personnel and the civilian population and is often followed by a heterogeneous array of clinical, cognitive, behavioral, mood, and neuroimaging changes. Unlike many neurological disorders that have a characteristic abnormal central neurologic area(s) of abnormality pathognomonic to the disorder, a sufficient head impact may cause focal, multifocal, diffuse or combination of injury to the brain. This inconsistent presentation makes it difficult to establish or validate biological and imaging markers that could help improve diagnostic and prognostic accuracy in this patient population. The purpose of this manuscript is to describe both the challenges and opportunities when conducting military-relevant TBI research and introduce the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Military Brain Injury working group. ENIGMA is a worldwide consortium focused on improving replicability and analytical power through data sharing and collaboration. In this paper, we discuss challenges affecting efforts to aggregate data in this patient group. In addition, we highlight how "big data" approaches might be used to understand better the role that each of these variables might play in the imaging and functional phenotypes of TBI in Service member and Veteran populations, and how data may be used to examine important military specific issues such as return to duty, the late effects of combat-related injury, and alteration of the natural aging processes.